Compositions adapted for use in controlled release delivery systems, such as biodegradable and bioerodible implants, are well known. Such controlled release systems are in general advantageous as they provide for the controlled and sustained release of medications, often directly at or near the desired site of action, over the period of days, weeks or even months.
Controlled release systems include polymer matrices that are known to be broken down in the body by various endogenous substances such as enzymes and water, such as polyesters including poly-lactide, poly-glycolide, polycaprolactone, and copolymers thereof, as well as capped versions using C1 to C10 mono-alkanols and chain-extended versions using C2 to C30 diols and polyols. Especially preferred are the “PLG copolymers” prepared from glycolide (1,4-dioxan-2,5-dione, glycolic acid cyclic dimer lactone) and lactide (3,6-dimethyl-1,4-dioxan-2,5-dione, lactic acid cyclic dimer lactone) as well as the capped and chain extended versions thereof. These copolymer materials are particularly favored for this application due to their facile breakdown in vivo by water or enzymes in the body to non-toxic materials, and their favorable properties in temporally controlling the release of biologically active agents (“bioactive agents”) that may be contained within a mass of the polymer.
These controlled release systems are typically prepared with a biocompatible polar aprotic organic liquid, injected into the body of a patient, and the biocompatible polar aprotic organic liquid dissipates to produce a solid or gel biodegradable implant. However, some biocompatible polar aprotic organic liquids may have unfavorable toxicological properties and/or cause irritation to the patient.
There is a continuing need to develop liquids, which have favorable toxicological properties and do not cause irritation to the patient, for the in situ formation of implants.